Pfizer Inc., San Diego, California, USA.
Ophthalmology. 2011 Oct;118(10):2022-7. doi: 10.1016/j.ophtha.2011.03.039. Epub 2011 Jul 23.
To evaluate short-term safety and steady-state systemic pharmacokinetics (PK) of latanoprost acid in pediatric subjects with glaucoma or ocular hypertension who received the adult latanoprost dose.
Phase 1, open-label, multicenter study.
Pediatric patients of 3 age groups (<3, 3-<12, and 12-<18 years) and adults (≥18 years) receiving latanoprost ophthalmic solution 0.005% once daily in 1 or both eyes for ≥2 weeks.
Latanoprost was administered in both eyes each morning post-screening. Subjects returned 3 to 28 days later for evaluation of plasma concentrations, withholding morning latanoprost. At the clinic, a single drop of latanoprost ophthalmic solution was instilled into both eyes. Plasma latanoprost acid concentrations were collected predose and 5, 15, 30, and 60 minutes after administration.
Latanoprost acid plasma exposure.
The evaluable PK analysis set included data from 39 of 47 enrolled subjects. The median peak plasma concentration value was higher in the <3-year age group (166 pg/ml) versus other groups (49, 16, and 26 pg/ml for the 3-<12-year, 12-<18-year, and ≥18-year age groups, respectively). The median area under the concentration-time curve from zero to last measurable concentration value was also higher in the <3-year age group (2716 pg/min/ml) versus other groups (588, 106, and 380 pg/min/ml for the 3-<12-year, 12-<18-year, and ≥18-year age groups, respectively). Latanoprost acid was rapidly eliminated from the blood, with plasma concentrations undetectable within 10 to 30 minutes postdose in all but the <3-year age group. There were no discontinuations or dose reductions due to adverse events or treatment-emergent adverse events.
Latanoprost acid systemic exposure was higher in younger children versus adolescents and adults, attributed primarily to lower body weight and smaller blood volume. Latanoprost acid was eliminated rapidly in all age groups and resulted in only a brief period of systemic exposure after once-daily dosing. Higher systemic exposure was not accompanied by adverse events, and on the basis of extrapolation of safety data from adults, this pilot study suggests an adequate safety margin for systemic adverse effects with use of the adult topical dose of latanoprost in pediatric patients.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.
评估接受成人拉坦前列素剂量的青光眼或高眼压儿童患者中拉坦前列素酸的短期安全性和稳态系统药代动力学（PK）。
1 期、开放标签、多中心研究。
接受单眼或双眼拉坦前列素滴眼液 0.005%，每日 1 次，持续≥2 周的 3 个年龄组（<3 岁、3-<12 岁和 12-<18 岁）的儿科患者和≥18 岁的成年人。
筛查后每天早晨在双眼给予拉坦前列素。3 至 28 天后，受试者返回评估血浆浓度，停止早晨使用拉坦前列素。在诊所，将单滴拉坦前列素滴眼液滴入双眼。在给药前和给药后 5、15、30 和 60 分钟采集血浆拉坦前列素酸浓度。
拉坦前列素酸的血浆暴露。
可评估的 PK 分析集包括 47 名入组患者中的 39 名患者的数据。<3 岁年龄组的中位峰血浆浓度值（166 pg/ml）高于其他组（3-<12 岁、12-<18 岁和≥18 岁年龄组分别为 49、16 和 26 pg/ml）。<3 岁年龄组的零至最后可测量浓度值的 AUC0-t 也高于其他组（3-<12 岁、12-<18 岁和≥18 岁年龄组分别为 2716、588、106 和 380 pg/min/ml）。拉坦前列素酸从血液中迅速消除，除<3 岁年龄组外，所有年龄组在给药后 10 至 30 分钟内血浆浓度均无法检测到。没有因不良事件或治疗中出现的不良事件而停药或减少剂量。
与青少年和成年人相比，年幼儿童的拉坦前列素酸全身暴露量更高，主要归因于体重较低和血容量较小。所有年龄组的拉坦前列素酸均迅速消除，每日 1 次给药后仅短暂暴露于全身。更高的全身暴露量并未伴随不良事件，并且基于从成年人外推的安全性数据，本初步研究表明，在儿科患者中使用成人局部剂量的拉坦前列素具有足够的全身不良反应安全裕度。
金融披露（Financial Disclosure(s)）：可能在参考文献后找到专有或商业披露信息。
